Trauma switch protecting us from fear identified

Researchers have identified a trauma switch that protects us from developing irrational and uncontrollable fear.

Our brains have the extraordinary capacity to adapt to changing environments, which includes protecting us from developing mental disorders, triggered by stress and trauma.

Stressful events re-programme certain receptors in the brain’s emotional centre, the amygdala, which then determines how the brain reacts to the next traumatic event, the journal Molecular Psychiatry reports.

These receptors, called PAR1, act in the same way as a command centre, telling neurons (brain cells) whether they should stop or accelerate their activity.

“The discovery that the same receptor can either awaken neurons or ‘switch them off,’ depending on previous trauma and stress experience, adds an entirely new dimension to our knowledge of how the brain operates and emotions are formed,” said professor Robert Pawlak from the University of Exeter Medical School, who led the study.

This helps us rein in exaggerated responses to mild or irrelevant fear triggers – for example, someone who may have witnessed a road accident, develops a fear of cars, according to an Exeter statement.

Before a traumatic event, PAR1s usually tell amygdala neurons to remain active and produce vivid emotions. However, after a trauma they command these neurons to switch off, so protecting us from developing uncontrollable fear.

The researchers used mice in which the PAR1 receptors were genetically de-activated and found that the animals developed a pathological fear in response to even mild stimuli.

Scientific Summary from Pubmed:
Fear memories are acquired through neuronal plasticity, an orchestrated sequence of events regulated at circuit and cellular levels. The conventional model of fear acquisition assumes unimodal (for example, excitatory or inhibitory) roles of modulatory receptors in controlling neuronal activity and learning. Contrary to this view, we show that protease-activated receptor-1 (PAR1) promotes contrasting neuronal responses depending on the emotional status of an animal by a dynamic shift between distinct G protein-coupling partners. In the basolateral amygdala of fear-naive mice PAR1 couples to G?q/11 and G?o proteins, while after fear conditioning coupling to G?o increases. Concurrently, stimulation of PAR1 before conditioning enhanced, but afterwards it inhibited firing of basal amygdala neurons. An initial impairment of the long-term potentiation (LTP) in PAR1-deficient mice was transformed into an increase in LTP and enhancement of fear after conditioning. These effects correlated with more frequent 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA) receptor-mediated miniature post synaptic events and increased neuronal excitability. Our findings point to experience-specific shifts in PAR1–G protein coupling in the amygdala as a novel mechanism regulating neuronal excitability and fear.